Studies on cycloaddition of cyclohexa-2,4-dienones and transformation of adducts: A general, stereoselective route to multifunctional bicyclo[2.2.2]octanes and diquinanes

Article abstract of DOI:10.1055/s-2008-1067203

The cycloaddition of in situ generated cyclohexa-2,4-di-enones with vinyl ethers, vinyl acetate, and phenyl vinyl sulfone leading to variously functionalized bicyclo[2.2.2]octanes has been examined. Functional group manipulation in the resulting adducts gave bicyclo[2.2.2]octanes endowed with a β,γ-enone chromophore. Triplet-sensitized irradiation of bicyclooctenones followed by reductive cleavage provided a stereoselective route to diquinane frameworks having diverse functionalities. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067203

PAPER
2719
Studies on Cycloaddition of Cyclohexa-2,4-dienones and Transformation of
Adducts: A General, Stereoselective Route to Multifunctional
Bicyclo[2.2.2]octanes and Diquinanes
C
ycloaddition of
C
i
yclohe
s
xa-2,4-die
h
nones and
T
w
ransformation of
A
a
dducts karma Singh,*a Girish Chandra,a Shaikh M. Mobinb
a
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India
b
National Single X-ray Diffraction Facility, Indian Institute of Technology Bombay, Mumbai 400076, India
E-mail: vks@chem.iitb.ac.in
Received 11 March 2008; revised 30 April 2008
In continuation of our studies, we further considered
examining the cycloadditions of 6-(chloromethyl)-6-hy-
droxycyclohexa-2,4-dienones with a range of dienophiles,
such as vinyl ethers, vinyl acetates, and vinyl phenyl sul-
Abstract: The cycloaddition of in situ generated cyclohexa-2,4-di-
enones with vinyl ethers, vinyl acetate, and phenyl vinyl sulfone
leading to variously functionalized bicyclo[2.2.2]octanes has been
examined. Functional group manipulation in the resulting adducts
gave bicyclo[2.2.2]octanes endowed with a b,g-enone chro- fone, so as to explore their reactivity and also develop a
mophore. Triplet-sensitized irradiation of bicyclooctenones fol-
stereoselective route to novel bicyclo[2.2.2]octanes of
lowed by reductive cleavage provided a stereoselective route to
diquinane frameworks having diverse functionalities.
type 2 since bicyclo[2.2.2]octanes are versatile synthetic
precursors.6 There are only a few routes to bicyclooctanes
Key words: Diels–Alder reaction, photochemistry, pericyclic reac-
tion, rearrangements
containing a b,g-enone chromophore. It was also thought
that the oxa-di-p-methane rearrangement of 2 would pro-
vide a stereoselective entry to diquinanes of type 3a,b
having distinguishable functional groups at central car-
The p4s+p2s cycloaddition reaction is one of the most
powerful synthetic methodologies by virtue of its diversi-
ty, versatility, and adaptability.1 Recently, the cycloaddi-
tion of species derived from oxidative dearomatization of
phenols such as o-benzoquinone masked ketals,2,3 and
spiroepoxycyclohexa-2,4-dienones4,5 has stimulated in-
tense interest since it provides molecular structures that
are otherwise not readily accessible. 6-(Chloromethyl)-6-
hydroxycyclohex-2,4-dienones of type 1 (Figure 1) con-
stitute interesting 4p systems and generally undergo cy-
cloaddition with electron rich dienophiles.5 Recently, we
have shown that these species, though electron deficient,
undergo efficient cycloadditions even with electron-poor
dienophiles such as acrylates.5b,c
bons of the five-membered rings, which are potential pre-
cursors to carbacyclins such as 4.7–9
Moreover, diquinanes, in general, have elicited sustained
interest10 due their synthetic potential and the presence of
this moiety in many natural products.11 Though there are
several methods for the synthesis of diquinane frame-
works, there are only a few methods leading to diquinanes
of type 3.
We wish to report herein the stereoselective cycloaddition
of cyclohexadienones of type 1 and manipulation of ad-
ducts to bicyclooctenones of type 2. Photochemical reac-
tion of the bicyclo[2.2.2]octenones and subsequent
transformation to diquinanes of type 3a,b is also reported.
Towards our objective, we thought to generate the cyclo-
hexadienones of type 6 from dimers such as 5 by retro-
Diels–Alder reaction and to examine its cycloaddition
with ethyl vinyl ether. Thus, the dimer 5a, readily pre-
pared from salicyl alcohol12 was heated in the presence of
excess ethyl vinyl ether, which gave the endo-adduct 7a in
moderate yield, as a result of regio- and stereoselective
cycloaddition (Scheme 1). Similarly, the dimers 5b and 5c
were prepared from 2-(hydroxymethyl)-4,5-dimethylphe-
nol and 2-(hydroxymethyl)-4,6-dimethylphenol, respec-
tively, following an analogous procedure,12 and heated
with ethyl vinyl ether. Thus, while the dimer 5b gave the
endo-adduct 7b exclusively, a mixture of endo- and exo-
adducts 7c (2:3) was obtained in the case of 5c. Interest-
ingly, the pyrolysis of 5a,b in the presence of butyl vinyl
ether also gave endo-adducts 8a,b selectively, in better
yields. Similarly, heating the dimer 5c with butyl vinyl
ether gave adducts 8c as a mixture of endo- and exo-iso-
mers, in good yields (Scheme 1). Though it is not clear at
the moment, the formation of the exo-isomer in the case of
R2
R1
O
O
Cl
OH
O
X
X
R
1
2
3a
CO2H
n
HO
OR
O
CO2Et
4
FG
3b
R
Figure 1
SYNTHESIS 2008, No. 17, pp 2719–2728
Advanced online publication: 24.07.2008
DOI: 10.1055/s-2008-1067203; Art ID: T03908SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
8

2720
V. Singh et al.
PAPER
6c could be due to steric interactions between the methyl enone was found to be more reactive and furnished
group and the ether moiety of the dienophile. The struc- adducts 9c, and 10c in good yield. The loss of endo selec-
tures of all adducts were deduced from their spectral data tivity in the cycloaddition with vinyl acetate is presum-
and comparison with known data. The configuration of ably due to steric effects and lack of strong secondary
adduct 7b was further confirmed by X-ray single crystal orbital interactions. Such behavior of vinyl acetate during
analysis (Figure 2).13
cycloadditions is known.4a
Cl
Cl
Cl
Cl
OH
HB
OAc
HC
HA
OH
HB
HA
HC
OH
OH
O
O
O
Cl
OH
O
R3
R3
R3
R2
OBu
∆
R3
5a–c
+
R3
O
R2
R1
R2
H
∆
R1
OAc
R1
5a–c
R2
R1
OAc
R1
OBu
R2
a R1 = H, R2 = H, R3 = H
b R1 = H, R2 = Me, R3 = Me
c R1 = Me, R2 = H, R3 = Me
9a (22%)
9b (30%)
9c (40%)
10a (28%)
10b (26%)
10c (40%)
a R1 = H, R2 = H, R3 = H
b R1 = H, R2 = Me, R3 = Me
c R1 = Me, R2 = H, R3 = Me
8a (52%)
8b (52%)
8c (67%, endo/
exo, 2:3)
∆
Scheme 2
Cl
O
OH
H
Cl
OH
O
R1
We further explored the interception of 6-(chloromethyl)-
6-hydroxycyclohexa-2,4-dienones 6a–c with phenyl vinyl
sulfone, a rarely used dienophile. Indeed, heating the
dimer 5c with phenyl vinyl sulfone ensued a smooth reac-
tion and furnished a single endo-adduct 11c in excellent
yield (80%) as a result of regio- and stereoselective cy-
cloaddition (Scheme 3). The structure of the adduct was
deduced from 1H and 13C NMR spectra and the endo ori-
entation of the sulfone group was revealed from the
COSY spectrum and further confirmed by single crystal
X-ray structure determination (Figure 3).14 Cycloaddition
of phenyl vinyl sulfone with cyclohexadienones generat-
ed from the other dimers 5a,b also exclusively gave the
corresponding endo-adducts in good yields (Scheme 3).
OEt
R3
7a (37%)
7b (37%)
7c (80%, endo/
exo, 2:3)
R2
R2
R1
OEt
R3
7a–c
6a–c
Scheme 1
Cl
SO2Ph
OH
O
R3
5a–c
o-dichlorobenzene
H
150 °C
R2
R1
SO2Ph
Figure 2 ORTEP diagram of compound 7b
a R1 = H, R2 = H, R3 = H
11a (46%)
b R1 = H, R2 = Me, R3 = Me
11b (56%)
c R1 = Me, R2 = H, R3 = Me
In order to extend the scope and generality, the above cy-
cloaddition was also attempted with vinyl acetate, which
is a poorly activated dienophile. Thus, when dimer 5a was
pyrolyzed in the presence of vinyl acetate in a sealed tube
at 140 °C, it provided a mixture of adducts in good yield
from which the endo- 9a and exo-isomers 10a (1.1:1)
were isolated by chromatography. The endo- and exo-ste-
reoisomers were distinguished by the chemical shift and
coupling constants of HA, HB, and HC. In general, the pro-
ton HA in the endo-isomer appears downfield (compared
to the exo-isomer). This is in agreement with an anisotro-
pic shielding of the endo proton by the C5=C6 double
bond.4a These trends were also observed for the other pairs
of isomers.
11c (80%)
Scheme 3
Heating the dimers 5b and 5c in the presence of vinyl ac-
etate also furnished the corresponding adducts 9b,c and
10b,c respectively (Scheme 2). Here again the cyclohexa-
dienone 6c having methyl groups at C2 and C4 of the di-
Figure 3 ORTEP diagram of compound 11c
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

PAPER
Cycloaddition of Cyclohexa-2,4-dienones and Transformation of Adducts
2721
The presence of the chloromethyl and hydroxy groups in gassed acetone (both solvent and sensitizer) was irradiat-
the above adducts provided further opportunities for ed under nitrogen with a mercury vapor lamp (125 W,
manipulation. Thus, treatment of adduct 8a with aqueous APP) during which a clean reaction occurred. Removal of
potassium hydroxide in the presence of cetyltrimethylam- the solvent followed by chromatography furnished the
monium bromide (CTAB) as a phase-transfer catalyst photoproduct 21, whose structure was deduced from its
gave the keto epoxide 12 in very good yield (Scheme 4).
spectral features and comparison with its precursor. Sim-
ilar irradiation of other chromophoric systems 16, 18, and
20 also gave the corresponding oxa-di-p-methane prod-
ucts 22–24 respectively, in reasonably good yields
(Scheme 6).
O
Cl
O
OH
O
O
O
R3
aq KOH
CTAB
CHCl3
0 °C to r.t.
R2
R1
SO2Ph
OBu
Cl
OBu
Cl
OH
OH
H
H
13, R1 = R2
=
O
8a
12
(83%)
R3 = H (84%)
hν
O
OAc
14, R1 = Me, R2 = H,
Pyrex
acetone
R
3 = Me (85%)
OAc
H
Scheme 4
9a
21 (45%)
H
Similarly, other chloromethyl-hydroxy adducts 11a and
11c were also converted into the keto epoxides 13 and 14,
respectively (Scheme 4).
O
SO2Ph
O
OBu
R1
R2
H
22 (44%)
23 R1 = R2 = H (60%)
24 R1 = R2 = Me (32%)
Further, reduction of 12 with zinc/ammonium chloride in
aqueous methanol at ambient temperature selectively fur-
nished the b-keto alcohol 15 (79%, as a mixture of syn/
Scheme 6
1
anti-isomers, H NMR) as the major product. Oxidation
of the b-keto alcohol 15 with Jones reagent followed by
decarboxylation gave ketone 16 (Scheme 5). Similarly,
the keto epoxides 13 and 14 were also transformed into
the keto sulfones 18 and 20, respectively, via the corre-
sponding b-keto alcohols 17 and 19.
A simplified mechanism for the oxa-di-p-methane reac-
tion is presented in Scheme 7. The triplet sensitized irra-
diation of a b,g-enone such as I proceeds through initial
formation of the species II, which rearranges to the dirad-
ical III that upon ring closure gives the photoproduct IV
(Scheme 7).
OH
O
O
H
O
1. Jones
reagent
O
Zn-NH4Cl
FG
FG
aq MeOH
r.t.
2. aq THF
∆
hν
O
OBu
16 (66%)
OBu
OBu
12
15 (79%)
I
IV
O
OH
H
hν
O
O
R2
R2
FG
FG
.
FG
R1
R1
.
SO2Ph
17, R1 = R2 = H (70%)
19, R1 = R2 = Me (74%)
SO2Ph
18 R1 = R2 = H (46%)
20, R1 = R2 = Me (50%)
.
O
O.
O
III
IV
II
Scheme 5
Scheme 7
Photoreactions of b,g-enones have generated significant
interest recently due to their synthetic applications.15–17 In
general, the sensitized irradiation of rigid b,g-enones
causes a 1,2-acyl shift or oxa-di-p-methane rearrange-
ment and direct irradiation leads to a 1,3-acyl shift. Dur-
ing their seminal studies on the photoreactions of b,g-
enones, Demuth and co-workers examined 1,2-acyl shifts
in some bicyclo[2.2.2]octanes and demonstrated their
synthetic potential.15a,b However, the photoreactions of
compounds of type 9, 18, and 20 have not been previously
explored. We first examined the photoreaction of 9a upon
sensitized irradiation. Thus, a solution of ketone 9a in de-
The photoproduct 22 was further manipulated to give the
functionalized diquinanes 25–28. Ketone 22 was alkylat-
ed with diethyl carbonate to give compound 25 as a mix-
ture of stereoisomers containing the isomer having a b-
ethoxycarbonyl group as the major product. Subsequent
treatment of 25 with tributyltin hydride/2,2¢-azobis(isobu-
tyronitrile)18 furnished the keto ester 26, as a mixture with
its enol tautomer 27 (1H NMR, 13C NMR). Ketone 22 was
also treated with tributyltin hydride/2,2¢-azobis(isobuty-
ronitrile) to give the diquinane 28 (Scheme 8). The
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

2722
V. Singh et al.
PAPER
EtO2C
O
1H NMR (400 MHz, CDCl3): d = 6.61 (superimposed dd, J = 8.5
Hz, 1 H), 6.14 (superimposed dd, J = 6.1 Hz, 1 H), 4.08–3.98 (m, 1
H), 3.72–3.38 (set of complex multiplets, 5 H), 3.24–3.16 (m, 1 H),
2.78 (br s, 1 H), 2.64 (ddd, J1 = 10.9 Hz, J2 = 8.5 Hz, J3 = 2.4 Hz, 1
H), 1.37–1.34 (dt, J1 = 6.1 Hz, J2 = 3.6 Hz, 1 H), 1.17 (t, J = 7.3 Hz,
3 H).
H
H
Bu3SnH
NaH
22
O
OBu
OBu
AIBN
benzene
∆, 12 h
THF
EtO2CO
H
H
25 (56%)
28 (67%)
13C NMR (100 MHz, CDCl3): d = 208.5, 135.4, 126.0, 75.6, 73.2,
64.4, 53.5, 50.8, 39.2, 29.1, 15.4.
HRMS (ESI): m/z [M + Na]+ calcd for C11H15ClNaO3: 253.0607;
found: 253.0598.
Bu3SnH
AIBN, benzene
∆, 12 h
EtO2C
EtO2C
H
H
H
+
HO
OBu
O
OBu
3-(Chloromethyl)-7-endo-ethoxy-3-hydroxy-5,6-dimethylbicy-
clo[2.2.2]oct-5-en-2-one (7b)
27
H
26
(73%)
Following the typical procedure for 7a using 5b (0.5 g, 1.34 mmol),
ethyl vinyl ether (5 mL), and o-dichlorobenzene (5 mL) and heating
at 130 °C for 20 h. Chromatography of the mixture (PE–EtOAc,
92:8) gave 7b (0.256 g, 37%) as a solid; mp 97–99 °C.
Scheme 8
diquinanes 26–28 are potential precursors for the synthe-
IR (KBr): 3452, 1707 cm–1.
sis of a variety of compounds including carbacyclins.9a,19
1H NMR (300 MHz, CDCl3): d = 3.98 (dt, J1 = 6.1 Hz, J2 = 3.0 Hz,
1 H), 3.63 (part of an AB pattern, JAB = 11.8 Hz, 1 H), 3.6–3.36
(cluster of multiplet, 4 H), 2.88 (superimposed dd, J = 2.6 Hz, 1 H),
2.55 (ddd, J1 = 10.9 Hz, J2 = 8.3 Hz, J3 = 2.6 Hz, 1 H), 2.4 (br s, 1
H), 1.9 (d, J = 1.3 Hz, 3 H), 1.78 (d, J = 1.3 Hz, 3 H), 1.3 (dt,
J1 = 13.6 Hz, J2 = 3.0 Hz, 1 H), 1.17 (t, J = 7.0 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 208.1, 134.9, 125.3, 75.9, 73.3,
64.3, 58.7, 50.1, 44.4, 29.0, 17.7, 17.1, 15.4.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19ClNaO3: 281.0920;
found: 281.0930.
In summary, we have demonstrated that cyclohexa-2,4-
dienones 6a–c are versatile 4p-partners and undergo
Diels–Alder reactions with a variety of dienophiles lead-
ing to multifunctional bicyclo[2.2.2]octenones 7a–c to
11a–c. This method is flexible, readily adaptable and per-
mits the introduction of various substituents on the bicyc-
lo[2.2.2]octane framework. Manipulation of the adducts
provided other functionalized bicyclo[2.2.2]octenones
12–20, which are otherwise not easily available. Triplet-
sensitized photochemical reaction of bicyclooctenones
9a, 16, 18, and 20 provided functionalized diquinane 3-(Chloromethyl)-7-endo-ethoxy-3-hydroxy-1,5-dimethylbicy-
clo[2.2.2]oct-5-en-2-one (7c)
Following the typical procedure for 7a using 5c (0.5 g, 1.34 mmol),
ethyl vinyl ether (5 mL), and o-dichlorobenzene (5 mL) and heating
at 125 °C for 12 h. Chromatography of the mixture (PE–EtOAc,
94:6) gave 7c (0.558 g, 80%) as an oily liquid as a inseparable mix-
frameworks 21, 22, 23, and 24 respectively, in stereose-
lective fashion. Alkylation and radical-induced cleavage
of the peripheral cyclopropane bond furnished diquinanes
26–28, which are versatile synthetic intermediates.
ture of endo- and exo-adducts (2:3).
IR spectra were recorded on a Nicolet Impact 400 FT-IR. 1H NMR
(300 MHz) and 13C (75 MHz) were recorded on a Varian VXR 300.
1H NMR (400 MHz) and 13C (100 MHz) were recorded on a Mer-
cury Varian 400 MHz. The samples were dissolved in CDCl3 with
TMS as internal standard. HRMS were recorded on a Q-Tof micro
(YA-105). Melting points were determined on a Veego apparatus of
Buchi type and are uncorrected. All organic extracts were dried over
anhyd Na2SO4. Reactions were monitored with TLC and spots were
visualized with I2 vapor. Column chromatography was performed
using SRL/Thomas Baker silica gel (60–120 and 100–200 mesh)
with elution using PE [petroleum ether (bp 60–80 °C)] and EtOAc
mixtures.
IR (neat): 3491, 1705 cm–1.
1H NMR (300 MHz, CDCl3) (signals for the major isomer):
d = 5.47–5.39 (m, 1 H), 3.72–3.34 (cluster of multiplet, 5 H), 2.98–
2.94 (m, 1 H), 2.63 (ddd, J1 = 11 Hz, J2 = 8.0 Hz, J3 = 2.9 Hz, 1 H),
2.47 (br s, 1 H), 1.95 (d, J = 1.8 Hz, 3 H), 1.44 (dt, J1 = 6.5 Hz,
J2 = 3.2 Hz, 1 H), 1.29 (s, 3 H), 1.15 (t, J = 6.9 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 209.6, 144.4, 123.7, 79.2, 73.2,
65.5, 58.0, 50.3, 43.0, 38.2, 21.0, 18.1, 15.4.
HRMS (ESI): m/z [M + Na]+ calcd for C13H19ClNaO3: 281.0920;
found: 281.0925.
7-endo-Butoxy-3-(chloromethyl)-3-hydroxybicyclo[2.2.2]oct-5-
en-2-one (8a)
Following the typical procedure for 7a using 5a (0.5 g, 1.57 mmol),
o-dichlorobenzene (5 mL), and butyl vinyl ether (4 mL, excess) and
heating at 140 °C for 20 h under N2. Chromatography (PE–EtOAc,
96:4) gave 8a (0.418 g, 52%) as a thick liquid.
3-(Chloromethyl)-7-endo-ethoxy-3-hydroxybicyclo[2.2.2]oct-5-
en-2-one (7a); Typical Procedure
Chlorohydroxy dimer 5a (1.0 g, 3.14 mmol) was taken up in a
round-bottomed flask fitted with a reflux condenser through which
cold H2O was circulated and o-dichlorobenzene (8 mL) was added.
An inert atmosphere was created by displacement of air by N2 and
freshly distilled ethyl vinyl ether (10 mL, excess) was added to the
mixture. The mixture was heated at 125 °C for 14 h with stirring
during time which more ethyl vinyl ether was added at regular in-
tervals. The mixture was brought to r.t. and charged as such on to a
column (silica gel, 60–120 mesh). Elution with PE gave o-dichlo-
robenzene. Continued elution with PE–EtOAc (9:1) gave 7a (0.540
g, 37%) as a solid; mp 102–103 °C.
IR (neat): 3455, 1734 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.60 (superimposed dd, J = 7.3
Hz, 1 H), 6.12 (superimposed dd, J = 7.3 Hz, 1 H), 4.02–3.98 (m, 1
H), 3.66–3.65 (m, 1 H), 3.63–3.52 (m, 2 H), 3.54–3.33 (m, 2 H),
3.22–3.16 (m, 1 H), 3.0–2.9 (br s, 1 H), 2.63 (ddd, J1 = 10.9 Hz,
J2 = 8.5 Hz, J3 = 2.4 Hz, 1 H), 1.54–1.47 (m, 2 H), 1.39–1.30 (m, 3
H), 0.90 (t, J = 7.3 Hz, 3 H).
IR (KBr): 3442, 1726 cm–1.
13C NMR (75 MHz, CDCl3): d = 208.6, 135.3, 125.8, 75.6, 73.1,
68.7, 53.3, 50.5, 39.0, 31.7, 28.9, 19.2, 13.8.
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

PAPER
Cycloaddition of Cyclohexa-2,4-dienones and Transformation of Adducts
2723
HRMS (ESI): m/z [M + Na]+ calcd for C13H19ClNaO3: 281.0920;
H), 2.79 (ddd, J1 = 10.9 Hz, J2 = 8.5 Hz, J3 = 2.3 Hz, 1 H), 2.7 (br s,
found: 281.0914.
1 H), 2.01 (s, 3 H), 1.36 (dt, J1 = 6.6 Hz, J2 = 3.5 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 206.0, 170.3, 136.2, 125.8, 72.6,
69.6, 53.0, 50.5, 38.8, 28.7, 21.1.
HRMS (ESI): m/z [M + Na]+ calcd for C11H13ClNaO4: 267.0190;
found: 267.0200.
7-endo-Butoxy-3-(chloromethyl)-3-hydroxy-5,6-dimethylbicy-
clo[2.2.2]oct-5-en-2-one (8b)
Following the typical procedure for 7a using 5b (0.1 g, 0.268
mmol), butyl vinyl ether (2 mL, excess), and o-dichlorobenzene (3
mL) and heated at 130 °C for 10 h. Chromatography of the mixture
(PE–EtOAc, 95:5) gave 8b (0.08 g, 52%) as a thick liquid.
exo-Adduct 10a
Mp 80–82 °C.
IR (KBr): 3501, 1739 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.60 (superimposed dd, J = 7.3
Hz, 1 H), 6.18 (superimposed dd, J = 7.3 Hz, 1 H), 5.16–4.96 (m, 1
H), 3.67 (part of an AB pattern, JAB = 12 Hz, 1 H), 3.55 (part of an
AB system JAB = 12 Hz, 1 H), 3.54–3.40 (m, 1 H), 3.27 (s, 1 H), 2.8
(br s, 1 H), 2.25–1.90 (m, 2 H), 2.05 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 206.8, 170.6, 137.8, 126.2, 73.9,
71.9, 52.2, 50.7, 39.3, 26.5, 21.1.
HRMS (ESI): m/z [M + H]+ calcd for C11H14ClO4: 245.0581; found:
245.0574.
IR (neat): 3431, 1719 cm–1.
1H NMR (300 MHz, CDCl3) d = 3.93 (dt, J1 = 5.8 Hz, J2 = 2.9 Hz,
1 H), 3.66–3.58 (m, 1 H), 3.48–3.28 (cluster of m, 4 H), 3.0 (s, 1 H),
2.86 (superimposed dd, J = 2.9 Hz, 1 H), 2.52 (ddd, J1 = 10.9 Hz,
J2 = 8.4 Hz, J3 = 2.5 Hz, 1 H), 1.87 (s, 3 H), 1.86 (s, 3 H), 1.54–1.42
(m, 2 H), 1.40–1.22 (m, 3 H), 0.87 (t, J = 7.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 208.5, 135.0, 125.2, 76.0, 73.3,
68.7, 58.7, 49.9, 44.3, 31.8, 28.8, 19.2, 17.6, 17.0, 13.8.
HRMS (ESI): m/z [M + K]+ calcd for C15H23ClKO3: 325.0973;
found: 325.0965.
7-endo-Butoxy-3-(chloromethyl)-3-hydroxy-1,5-dimethylbicy-
clo[2.2.2]oct-5-en-2-one (8c)
7-endo-Acetoxy-3-(chloromethyl)-3-hydroxy-5,6-dimethylbicy-
clo[2.2.2]oct-5-en-2-one (9b) and 7-exo-Acetoxy-3-(chlorometh-
yl)-3-hydroxy-5,6-dimethylbicyclo[2.2.2]oct-5-en-2-one (10b)
Following the typical procedure for 10a using 5b (0.5 g, 1.34
mmol), vinyl acetate (3 mL), and o-dichlorobenzene (2 mL) and
heating at 150 °C for 17 h. The mixture was charged on a small pad
of silica gel and washed with PE to remove the solvent and excess
dienophile. Elution with PE–EtOAc (75:25) gave the mixture of ad-
ducts (TLC) which was further chromatographed on silica gel (100–
200 mesh). Elution with PE–EtOAc (93:7) first gave the endo-ad-
duct 9b (0.219 g, 30%). Further elution with PE–EtOAc (9:1) gave
the exo-adduct 10b (0.184 g, 26%) as a colorless solid.
Following the typical procedure for 7a using 5c (0.5 g, 1.34 mmol),
butyl vinyl ether (4 mL, excess), and o-dichlorobenzene (4 mL) and
heating at 120 °C for 6 h under N2. Chromatography of the mixture
(PE–EtOAc, 97:3) gave 8c (0.510 g, 67%) as a thick liquid as an in-
separable mixture of endo- and exo-adducts.
IR (neat): 3435, 1726 cm–1.
1H NMR (400 MHz, CDCl3) (signals due to major isomer):
d = 5.45–5.41 (m, 1 H), 3.87 (dt, J1 = 5.8 Hz, J2 = 2.7 Hz, 1 H),
3.72–3.68 (m, 1 H), 3.6 (part of an AB system, JAB = 12.0 Hz, 1 H),
3.5 (part of an AB system, JAB = 11.7 Hz, 1 H), 3.55–3.45 (m, 1 H),
3.38–3.27 (m, 1 H), 2.96 (s, 1 H), 2.6 (ddd, J1 = 10.9 Hz, J2 = 8.1
Hz, J3 = 2.7 Hz, 1 H), 1.94 (d, J = 1.5 Hz, 3 H), 1.56–1.48 (m, 2 H),
1.38–1.32 (m, 3 H), 1.29 (s, 3 H), 0.90 (t, J = 6.6 Hz, 3 H).
endo-Adduct 9b
Mp 92–94 °C.
13C NMR (100 MHz, CDCl3): d = 209.7, 131.8, 123.8, 79.4, 74.0,
IR (KBr): 3447, 1732, 1713 cm–1.
69.9, 58.1, 50.3, 43.1, 38.3, 32.0, 30.0, 21.1, 19.4, 14.1.
HRMS (ESI): m/z [M + Na]+ calcd for C15H23ClNaO3: 309.1233;
found: 309.1241.
1H NMR (300 MHz, CDCl3): d = 5.26 (dt, J1 = 6.2 Hz, J2 = 2.9 Hz,
1 H), 3.7 (part of an AB pattern, JAB = 12 Hz, 1 H), 3.46 (part of an
AB pattern JAB = 12 Hz, 1 H), 3.30 (d, J = 3.6 Hz, 1 H), 2.96 (super-
imposed dd, J = 2.9 Hz, 1 H), 2.70 (ddd, J1 = 10.9 Hz, J2 = 8.4 Hz,
J3 = 2.5 Hz, 1 H), 2.63 (br s, 1 H), 2.03 (s, 3 H), 1.92 (d, J = 1.0 Hz,
3 H), 1.76 (d, J = 1.0 Hz, 3 H), 1.35 (dt, J1 = 6.2 Hz, J2 = 2.9 Hz, 1
H).
13C NMR (75 MHz, CDCl3): d = 205.6, 170.3, 135.9, 125.4, 72.9,
70.4, 58.6, 50.0, 44.2, 28.5, 21.1, 17.7, 17.2.
HRMS (ESI): m/z [M + Na]+ calcd for C13H17ClNaO4: 295.0713;
found: 295.0709.
7-endo-Acetoxy-3-(chloromethyl)-3-hydroxybicyclo[2.2.2]oct-
5-en-2-one (9a) and 7-exo-Acetoxy-3-(chloromethyl)-3-hy-
droxybicyclo[2.2.2]oct-5-en-2-one (10a); Typical Procedure
A mixture of 5a (0.5 g, 1.57 mmol), and vinyl acetate (3 mL) in o-
dichlorobenzene (2 mL) was heated in a sealed tube at 140 °C for
20 h. The mixture was filtered through a small pad of silica gel and
eluted with PE to remove the solvent and excess dienophile. Elution
with PE–EtOAc (75:25) gave the mixture of adducts (TLC). The
mixture of adducts thus obtained was rechromatographed (silica gel
100–200 mesh). Elution with PE–EtOAc (91:9) first gave the endo-
adduct 9a (0.166 g, 22%) as a colorless solid. Further elution with
PE–EtOAc (9:1) gave the exo-adduct 10a (0.211 g, 28%) as a col-
orless solid.
exo-Adduct 10b
Mp 110–111 °C.
IR (KBr): 3490, 1744, 1723 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.08–5.0 (m, 1 H), 3.7 (part of an
AB system, JAB = 12 Hz, 1 H), 3.46 (part of an AB system, JAB = 12
Hz, 1 H), 3.18 (d, J = 3.6 Hz, 1 H), 2.96 (superimposed dd, J = 2.9
Hz, 1 H), 2.5 (br s, 1 H), 2.06–2.03 (m, merged with singlet, 2 H),
2.03 (s, 3 H), 1.87 (d, J = 1.0 Hz, 3 H), 1.76 (d, J = 1.0 Hz, 3 H).
endo-Adduct 9a
Mp 130–131 °C.
IR (KBr): 3471, 1739, 1713 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.63 (superimposed dd, J = 7.0
Hz, 1 H), 6.15 (superimposed dd, J = 7.0 Hz, 1 H), 5.36–5.27 (m, 1
H), 3.65 (part of an AB pattern, JAB = 12 Hz, 1 H), 3.61–3.56 (m, 1
H), 3.5 (part of an AB system JAB = 12 Hz, 1 H), 3.26–3.18 (m, 1
13C NMR (75 MHz, CDCl3): d = 206.9, 170.6, 138.2, 125.4, 74.2,
72.1, 58.0, 50.2, 45.0, 27.0, 21.2, 17.2, 16.5.
HRMS (ESI): m/z [M + Na]+ calcd for C13H17ClNaO4: 295.0503;
found: 295.0671.
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

2724
V. Singh et al.
PAPER
7-endo-Acetoxy-3-(chloromethyl)-3-hydroxy-1,5-dimethylbicy-
clo[2.2.2]oct-5-en-2-one (9c) and 7-exo-Acetoxy-3-(chlorometh-
yl)-3-hydroxy-1,5-dimethylbicyclo[2.2.2]oct-5-en-2-one (10c)
Following the typical procedure for 10a using 5c (0.5 g, 1.34
mmol), vinyl acetate (3 mL, excess), and o-dichlorobenzene (2 mL)
and heating at 140 °C for 12 h. Chromatography with elution with
PE–EtOAc (94:6) first gave the adduct 9c (0.290 g, 40%) as a col-
orless solid. Further elution with PE–EtOAc (9:1) gave the exo-ad-
duct 10c (0.293 g, 40%) as a colorless solid.
(PE–EtOAc, 78:22) gave 11b (0.240 g, 56%) as a colorless solid;
mp 158–159 °C.
IR (KBr): 3356, 1725 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.83–7.77 (m, 2 H), 7.63–7.55 (m,
1 H), 7.54–7.45 (m, 2 H), 3.62 (d, J = 11.9 Hz, 1 H), 3.57–3.50 (m,
1 H), 3.32–3.27 (m, 2 H), 3.0–2.95 (m, 1 H), 2.50 (s, 1 H), 2.25
(ddd, J1 = 13.1 Hz, J2 = 9.7 Hz, J3 = 3.0 Hz, 1 H), 1.83–1.74 (cluster
of m, 7 H).
13C NMR (100 MHz, CDCl3): d = 202.4, 138.2, 136.8, 134.1, 129.5,
128.5, 125.4, 73.1, 59.3, 52.5, 49.7, 44.7, 22.4, 17.25, 17.20.
endo-Adduct 9c
Mp 92–93 °C.
IR (KBr): 3442, 1729, 1265 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C17H19ClNaO4S: 377.0590;
found: 377.0591.
1H NMR (300 MHz, CDCl3): d = 5.47–5.42 (m, 1 H), 4.98 (ddd,
J1 = 4.3 Hz, J2 = 3.2 Hz, J3 = 1 Hz, 1 H), 3.68 (part of an AB sys-
tem, JAB = 12 Hz, 1 H), 3.46 (part of an AB system, JAB = 12 Hz, 1
H), 3.01–2.96 (m, 1 H), 2.84 (ddd, J1 = 10.9 Hz, J2 = 8.4 Hz,
J3 = 2.5 Hz, 1 H), 2.45 (br s, 1 H), 2.04 (s, 3 H), 1.98 (d, J = 1.8 Hz,
3 H), 1.33 (dt, J1 = 6.5, J2 = 3.2 Hz, 1 H), 1.21 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 207.6, 170.3, 145.2, 123.3, 73.5,
72.8, 53.6, 50.0, 43.0, 30.4, 20.9, 20.8, 13.8.
HRMS (ESI): m/z [M + Na]+ calcd for C13H17ClNaO4: 295.0713;
found: 295.0706.
3-(Chloromethyl)-3-hydroxy-1,5-dimethyl-7-endo-(phenylsul-
fonyl)bicyclo[2.2.2]oct-5-en-2-one (11c)
Following the typical procedure for 10a using 5c (0.1 g, 0.268
mmol), phenyl vinyl sulfone (0.068 g, 0.402 mmol), and o-dichlo-
robenzene (1.0 mL) and heating at 125 °C for 6 h. Chromatography
(PE–EtOAc, 80:20)] gave 11c (0.152 g, 80%) as a colorless solid;
mp 178–180 °C.
IR (KBr): 3453, 1729 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.88–7.83 (m, 2 H), 7.69–7.62 (m,
1 H), 7.60–7.54 (m, 2 H), 5.50 (s, 1 H), 3.69 (part of AB system,
J = 12.0 Hz, 1 H), 3.51 (dd, J1 = 9.75, J2 = 7.0 Hz, 1 H), 3.40 (part
of AB system, J = 12.0 Hz, 1 H), 3.01–2.98 (m, 1 H), 2.56 (s, 1 H),
2.26 (ddd, J1 = 13.6 Hz, J2 = 9.7 Hz, J3 = 2.7 Hz, 1 H), 1.90 (d,
J = 1.5 Hz, 3 H), 1.79 (ddd, J1 = 9.7 Hz, J2 = 7.0 Hz, J3 = 2.73 Hz,
1 H), 1.54 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 205.4, 144.5, 139.7, 133.83, 129.3,
128.5, 123.9, 72.8, 63.2, 50.6, 49.7, 43.1, 25.9, 20.7, 16.2.
HRMS (ESI): m/z [M + Na]+ calcd for C17H19ClNaO4S: 377.0590;
found: 377.0605.
exo-Adduct 10c
Mp 96–98 °C.
IR (KBr): 3451, 1735, 1265 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.42–5.39 (m, 1 H), 4.83 (dd,
J1 = 9.3 Hz, J2 = 3.1 Hz, 1 H), 3.71 (part of an AB pattern, JAB = 12
Hz, 1 H), 3.5 (part of an AB pattern, JAB = 12 Hz, 1 H), 3.02–2.99
(m, 1 H), 2.51 (br s, 1 H), 2.21–2.12 (m, 1 H), 2.06–1.97 (m, 4 H),
1.94 (d, J = 1.5 Hz, 3 H), 1.19 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 208.0, 170.6, 147.7, 123.5, 76.4,
73.6, 52.5, 50.0, 43.9, 28.4, 20.8, 20.6, 14.2.
HRMS (ESI): m/z [M + Na]+ calcd for C13H17ClNaO4: 295.0713;
8-endo-Butoxyspiro[bicyclo[2.2.2]oct-5-ene-2,2¢-oxiran]-3-one
(12); Typical Procedure
found: 295.0709.
To a soln of 8a (2.40 g, 9.28 mmol) in CHCl3 (200 mL) containing
CTAB (0.3 g) was added a soln of KOH (0.6 g, 10.7 mmol) in H2O
(25 mL). The mixture was stirred at r.t. (~30 °C) for 7 h, after which
the organic phase was separated and the aqueous layer extracted
with CHCl3 (3 × 25 mL). The combined organic extracts were
washed with brine and dried (anhyd Na2SO4). Removal of solvent
followed by column chromatography (silica gel, PE–EtOAc, 95:5)
gave 12 (1.7 g, 83%) as a colorless thick liquid.
3-(Chloromethyl)-3-hydroxy-7-endo-(phenylsulfonyl)bicy-
clo[2.2.2]oct-5-en-2-one (11a)
Following the typical procedure for 10a using 5a (1.0 g, 3.15
mmol), phenyl vinyl sulfone (0.8 g, 4.73 mmol), and o-dichloroben-
zene (5 mL) and heating at 150 °C for 22 h. Chromatography (silica
gel, 60–120 mesh) with continued elution with PE–EtOAc (80:20)
gave some unreacted dimer (0.200 g, 20%). Further elution with
PE–EtOAc (78:22) gave 11a (0.935 g, 46%) as a colorless solid; mp
130–132 °C.
IR (neat): 1736 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.68–6.61 (m, 1 H), 6.20–6.12 (m,
1 H), 4.10–4.02 (m, 1 H), 3.78–3.72 (m, 1 H), 3.52–3.34 (m, 2 H),
3.13 (d, J = 6.2 Hz, 1 H), 2.84 (d, J = 6.2 Hz, 1 H), 2.60–2.52 (m, 1
H), 2.52–2.44 (m, 1 H), 1.64–1.48 (m, 3 H), 1.42–1.28 (m, 2 H),
0.90 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 204.8, 134.6, 126.3, 75.2, 68.8,
57.7, 53.7, 53.5, 37.6, 31.8, 31.6, 19.3, 13.9.
IR (KBr): 3452, 1733 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.92–7.85 (m, 2 H), 7.74–7.67
(m, 1 H), 7.64–7.57 (m, 2 H), 6.56 (superimposed dd, J = 8.1 Hz, 1
H), 6.29–6.21 (m, 1 H), 3.73–3.65 (m, 3 H), 3.45 (d, J = 12 Hz, 1
H), 3.38–3.33 (m, 1 H), 2.65 (s, 1 H), 2.47 (ddd, J1 = 12.8 Hz,
J2 = 9.7 Hz, J3 = 3.1 Hz, 1 H), 1.95 (ddd, J1 = 9.3 Hz, J2 = 6.6 Hz,
J3 = 2.7 Hz, 1 H).
HRMS (ESI): m/z [M + Na]+ calcd for C13H18NaO3: 245.1154;
found: 245.1152.
13C NMR (75 MHz, CDCl3): d = 203.2, 138.0, 135.8, 134.3, 129.6
(2 C), 128.6 (2 C), 125.7, 72.9, 59.3, 50.3, 47.2, 39.3, 22.8.
HRMS (ESI): m/z [M + Na]+ calcd for C15H15ClNaO4S: 349.0277;
8-endo-(Phenylsulfonyl)spiro[bicyclo[2.2.2]oct-5-ene-2,2¢-oxi-
ran]-3-one (13)
found: 349.0287.
Following the typical procedure for 12 using 11a (1.27 g, 3.89
mmol), CHCl3 (120 mL), CTAB (0.125 g), and a soln of KOH
(0.350 g, 6.23 mmol) in H2O (25 mL) and stirring at r.t. (~30 °C) for
8 h. Column chromatography (silica gel, PE–EtOAc, 4:1) gave 13
(0.941 g, 84%) as a colorless solid; mp 168–170 °C.
3-(Chloromethyl)-3-hydroxy-5,6-dimethyl-7-endo-(phenylsul-
fonyl)bicyclo[2.2.2]oct-5-en-2-one (11b)
Following the typical procedure for 10a using 5b (0.230 g, 0.616
mmol), phenyl vinyl sulfone (0.142 g, 0.845 mmol), and o-dichlo-
robenzene (3 mL) and heating at 140 °C for 20 h. Chromatography
IR (KBr): 1736 cm–1.
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

PAPER
Cycloaddition of Cyclohexa-2,4-dienones and Transformation of Adducts
2725
1H NMR (300 MHz, CDCl3): d = 7.92–7.86 (m, 2 H), 7.74–7.67 (m,
1 H), 7.64–7.54 (m, 2 H), 6.67–6.6 (m, 1 H), 6.33–6.25 (m, 1 H),
3.78–3.74 (m, 1 H), 3.72–3.62 (m, 1 H), 3.17 (d, J = 5.8 Hz, 1 H),
2.88 (d, J = 6.2 Hz, 1 H), 2.56–2.5 (m, 1 H), 2.38 (ddd, J1 = 13.5 Hz,
J2 = 9.8 Hz, J3 = 2.9 Hz, 1 H), 2.22–2.14 (ddd, J1 = 10.9 Hz,
J2 = 6.2 Hz, J3 = 3.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 200.6, 137.9, 134.9, 134.2, 129.5,
128.4, 125.9, 59.3, 56.9, 52.9, 47.6, 37.7, 24.6.
HRMS (ESI): m/z [M + Na]+ calcd for C15H14NaO4S: 313.0511;
found: 313.0519.
solvent gave a b-keto acid that was directly subjected to decarbox-
ylation as described below. The b-keto acid thus obtained was taken
in THF–H2O (1:1, 120 mL) and the mixture was refluxed for 8 h.
THF was removed under vacuum and the aqueous medium was fur-
ther diluted with H2O and extracted with EtOAc (3 × 50 mL). The
combined extracts were washed with NaHCO3 soln, H2O, and brine
and dried (anhyd Na2SO4). Removal of solvent followed by chro-
matography (PE–EtOAc, 95:5) of the residue gave 16 (1.68 g, 66%)
as a colorless liquid.
IR (KBr): 1732 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.61 (superimposed dd, J = 7.6
Hz, 1 H), 6.07 (superimposed dd, J = 6.9 Hz, 1 H), 3.98–3.88 (m, 1
H), 3.62–3.58 (m, 1 H), 3.48–3.40 (m, 1 H), 3.38–3.30 (m, 1 H),
3.04–2.96 (m, 1 H), 2.13 (ddd, J1 = 10.9 Hz, J2 = 8.4 Hz, J3 = 2.5
Hz, 1 H), 2.05–1.98 (m, 1 H), 1.91–1.86 (m, 1 H), 1.54–1.44 (m, 3
H), 1.38–1.28 (m, 2 H), 0.89 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 211.8, 137.0, 125.1, 74.8, 68.7,
54.5, 39.7, 34.9, 31.9, 31.6, 19.4, 13.9.
HRMS (ESI): m/z [M + Na]+ calcd for C12H18NaO2: 217.1204;
4,6-Dimethyl-8-endo-(phenylsulfonyl)spiro[bicyclo[2.2.2]oct-5-
ene-2,2¢-oxiran]-3-one (14)
Following the typical procedure for 12 using 11c (3.8 g, 10.71
mmol), CHCl3 (200 mL), CTAB (0.2 g), and a soln of KOH (0.78
g, 13.92 mmol) in H2O (25 mL) and stirring for 8 h. Chromatogra-
phy (PE–EtOAc, 4:1) gave 14 (2.9 g, 85%) as a colorless solid; mp
186 °C.
IR (KBr): 1737 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.89–7.83 (m, 2 H), 7.69–7.63 (m,
1 H), 7.61–7.53 (m, 2 H), 5.52 (s, 1 H), 3.53 (dd, J1 = 10.2, J2 = 6.5
Hz, 1 H), 3.16 (part of AB pattern, JAB = 6.2 Hz, 1 H), 2.90 (part of
AB pattern, JAB = 6.2 Hz, 1 H), 2.32 (dd, J1 = 4.7 Hz, J2 = 2.5 Hz, 1
H), 2.20 (ddd, J1 = 13.8 Hz, J2 = 10.2 Hz, J3 = 2.9 Hz, 1 H), 2.02
(ddd, J1 = 9.1 Hz, J2 = 6.5 Hz, J3 = 2.5 Hz, 1 H), 1.87 (d, J = 1.4 Hz,
3 H), 1.56 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 202.6, 143.6, 139.9, 133.8, 129.3,
128.4, 124.4, 63.3, 56.8, 52.5, 51.4, 42.1, 27.8, 20.4, 16.3.
HRMS (ESI): m/z [M + Na]+ calcd for C17H18NaO4S: 341.0824;
found: 217.1199.
7-endo-(Phenylsulfonyl)bicyclo[2.2.2]oct-5-en-2-one (18)
Following the typical procedure for 15, using a suspension of acti-
vated zinc (18 g, excess) in MeOH–H2O (7:1, 80 mL), a soln of 13
(1.4 g, 4.82 mmol) in MeOH (20 mL), NH4Cl (2 g, excess) and stir-
ring at r.t. (~30 °C) for 10 h. Column chromatography (PE–EtOAc,
60: 40) gave 17 (0.980 g, 70%, mixture of syn/anti-isomers) as a
colorless liquid that was subjected to oxidation and decarboxyl-
ation.
To a soln of keto alcohol 17 (0.970 g, 3.32 mmol) in acetone (40
mL) was added dropwise freshly prepared Jones reagent with stir-
ring at 0 °C. After the reaction was complete (TLC, ~1 h) the sol-
vent was removed under vacuum and the residue was diluted with
H2O and extracted with EtOAc (4 × 50 mL). The combined extracts
were washed with H2O and brine and dried (anhyd Na2SO4). Re-
moval of solvent gave a b-keto acid, which was directly subjected
to decarboxylation. The b-keto acid thus obtained was taken in
THF–H2O (1:1, 44 mL) and the mixture was refluxed for 16 h. The
THF was removed under vacuum and the aqueous medium was fur-
ther diluted with H2O and extracted with EtOAc (3 × 50 mL). The
combined extracts were washed with NaHCO3 soln, H2O, and brine
and dried (anhyd Na2SO4). Removal of solvent followed by chro-
matography (PE–EtOAc, 90:10) gave 18 (0.400 g, 46%) as a color-
less solid; mp 120–121 °C.
found: 341.0833.
7-endo-Butoxy-3-(hydroxymethyl)bicyclo[2.2.2]oct-5-en-2-one
(15); Typical Procedure
To a suspension of activated Zn (13 g, excess) in MeOH–H2O (5:1,
90 mL) was added a soln of 12 (2.4 g, 10.8 mmol) in MeOH (10 mL)
followed by NH4Cl (2.6 g, excess) and the mixture was stirred at r.t.
(~30 °C) for 12 h. It was filtered through a Celite pad and the filtrate
was concentrated in vacuo and the residue was diluted with H2O and
extracted with EtOAc (3 × 50 mL). The combined extracts were
washed with brine and dried (Na2SO4). The solvent was removed
under reduced pressure and the product was purified by column
chromatography (PE–EtOAc, 80:20) to give 15 (1.9 g, 79%, mix-
ture of syn/anti-isomers) as a colorless liquid.
IR (KBr): 1740 cm–1.
IR (KBr): 1732 cm–1.
1H NMR (400 MHz, CDCl3): d = 6.74–6.50 (m, 2 H), 6.12–6.00
(m, 2 H), 4.0–3.80 (m, 2 H), 3.74–3.68 (m, 2 H), 3.64–3.50 (m, 6
H), 3.48–3.42 (m, 4 H), 3.38–3.30 (m, 4 H), 2.99–2.90 (m, 2 H),
2.60–2.50 (br s, 1 H), 2.30–2.12 (m, 3 H), 1.60–1.42 (m, 3 H), 1.40–
1.26 (m, 3 H), 0.98–0.94 (m, 6 H).
1H NMR (300 MHz, CDCl3): d = 7.90–7.85 (m, 2 H), 7.76–7.65 (m,
1 H), 7.66–7.55 (m, 2 H), 6.62–6.54 (m, 1 H), 6.19–6.10 (m, 1 H),
3.60–3.48 (m, 2 H), 3.20–3.12 (m, 1 H), 2.18–1.98 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 206.8, 138.3, 137.4, 134.2, 129.6,
128.8, 124.7, 59.2, 48.6, 38.6, 31.9, 27.8.
HRMS (ESI): m/z [M + H]+ calcd for C14H15O3S: 263.0742; found:
263.0739.
13C NMR (100 MHz, CDCl3): d = 213.9, 137.9, 125.0, 75.3, 68.6,
61.6, 54.4, 48.8, 34.9, 31.7, 29.9, 19.2, 13.8 (signals due to major
isomer).
HRMS (ESI): m/z [M + H]+ calcd for C13H21O3: 225.1491; found:
225.1492.
3-(Hydroxymethyl)-1,5-dimethyl-7-endo-(phenylsulfonyl)bicy-
clo[2.2.2]oct-5-en-2-one (19)
Following the typical procedure for 15 using activated Zn (21 g, ex-
cess), MeOH–H2O (5:1, 120 mL,) a soln of 14 (3.0 g, 9.4 mmol) in
MeOH (20 mL), and NH4Cl (3.5 g, excess) and stirring at r.t. (~30
°C) for 14 h. Chromatography (PE–EtOAc, 70:30) gave 19 (2.2 g,
74%, mixture of syn/anti-isomers) as a colorless solid; mp 176–177
°C.
7-endo-Butoxybicyclo[2.2.2]oct-5-en-2-one (16); Typical Proce-
dure
To a soln of 15 (3.0 g, 13.3 mmol) in acetone (60 mL) was added
dropwise freshly prepared Jones reagent with stirring at 0 °C. When
the reaction was complete (TLC, ~30 min), the solvent was re-
moved under vacuum and the residue was diluted with H2O and ex-
tracted with EtOAc (4 × 50 mL). The combined extracts were
washed with H2O and brine and dried (anhyd Na2SO4). Removal of
IR (KBr): 3432, 1721 cm–1.
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

2726
V. Singh et al.
PAPER
1H NMR (400 MHz, CDCl3) (major isomer): d = 7.87–7.80 (m, 2
H), 7.69–7.60 (m, 1 H), 7.60–7.52 (m, 2 H), 5.40 (s, 1 H), 3.75–3.25
(set of m, 3 H), 2.70–2.68 (m, 1 H), 2.28–2.24 (m, 1 H), 2.20–1.90
(set of m, 2 H), 1.86–1.74 (set of m, 4 H), 1.5 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C17H21O4S: 321.1161; found:
321.1154.
HRMS (ESI): m/z [M + H]+ calcd for C12H19O2: 195.1385; found:
195.1389.
7-exo-(Phenylsulfonyl)tricyclo[3.3.0.02,8]octan-3-one (23)
Following the typical procedure for 21, irradiation of a soln of 18
(0.100 g, 0.33 mmol) in acetone (110 mL) for 1.5 h followed by re-
moval of the solvent and chromatography (PE–EtOAc, 75:25) gave
23 (0.060 g, 60%) as a thick colorless liquid.
1,5-Dimethyl-7-endo-(phenylsulfonyl)bicyclo[2.2.2]oct-5-en-2-
one (20)
IR (neat): 1725 cm–1.
Following the typical procedure for 16 using 19 (0.5 g, 1.56 mmol)
in acetone (15 mL) was added dropwise a freshly prepared Jones re-
agent with stirring at 0 °C and the mixture was stirred for 1 h to give
a b-keto acid that was directly subjected to decarboxylation. The b-
keto acid thus obtained was taken up in THF–H2O (1:1, 22 mL) and
the mixture was refluxed for 16 h. THF was removed under vacuum
and the aqueous medium was further diluted with H2O and extracted
with EtOAc (3 × 25 mL). The combined extracts were washed with
NaHCO3 soln, H2O, and brine and dried (anhyd Na2SO4). Removal
of solvent followed by chromatography (PE–EtOAc, 88:12) gave
20 (0.225 g, 50%); mp 162–64 °C.
1H NMR (400 MHz, CDCl3): d = 7.95–7.88 (m, 2 H), 7.73–7.65 (m,
1 H), 7.63–7.55 (m, 2 H), 3.56–3.0 (m, 1 H), 3.12–3.04 (m, 1 H),
2.93 (dd, J1 = 10.9 Hz, J2 = 5.4 Hz, 1 H), 2.74–2.66 (m, 1 H), 2.56
(dd, J1 = 17.9 Hz, J2 = 9.5 Hz, 1 H), 2.42–2.34 (m, 1 H), 2.06–2.0
(m, 1 H), 1.82–1.74 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 212.8, 138.5, 134.1, 129.6, 128.6,
63.8, 47.2, 42.2, 37.4, 37.1, 35.6, 30.8.
HRMS (ESI): m/z [M + H]+ calcd for C14H15O3S: 263.0742; found:
263.0742.
1,8-Dimethyl-7-exo-(phenylsulfonyl)tricyclo[3.3.0.02,8]octan-3-
one (24)
IR (KBr): 1725 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.87–7.83 (m, 2 H), 7.68–7.62 (m,
1 H), 7.60–7.53 (m, 2 H), 5.35 (s, 1 H), 3.41 (dd, J1 = 9.7 Hz,
J2 = 7.4 Hz, 1 H), 2.71 (dd, J1 = 5.4 Hz, J2 = 2.3 Hz, 1 H), 2.19–2.01
(m, 2 H), 1.97–1.87 (m, 2 H), 1.80 (d, J = 1.5 Hz, 3 H), 1.50 (s, 3 H).
13C NMR (100 MHz, CDCl3): d = 208.0, 145.8, 140.0, 133.6, 129.1,
128.5, 123.0, 63.4, 51.0, 38.1, 36.0, 31.1, 19.8, 16.4.
Following the typical procedure for 21, irradiation of a soln of 20
(0.098 g, 0.337 mmol) in degassed acetone (110 mL) for 1.5 h fol-
lowed by removal of the solvent and chromatography (PE–EtOAc,
88:12) first gave the starting material (0.007 g, 7%). Further elution
(PE–EtOAc, 85:15) afforded 24 (0.03 g, 32%) as a colorless solid;
mp 128–129 °C.
HRMS (ESI): m/z [M + H]+ calcd for C16H19O3S: 291.1055; found:
IR (neat): 1716 cm–1.
291.1053.
1H NMR (300 MHz, CDCl3): d = 7.89–7.82 (m, 2 H), 7.69–7.62 (m,
1 H), 7.60–7.52 (m, 2 H), 3.56 (dd, J1 = 11.3 Hz, J2 = 5.8 Hz, 1 H),
2.74–2.52 (m, 3 H), 1.62 (s, 1 H), 1.55 (s, 3 H), 1.47 (s, 3 H), 1.27
(dd, J1 = 17.2 Hz, J2 = 5.8 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 212.8, 139.7, 133.8 (2 C), 129.3 (2
C), 128.3, 67.2, 51.0, 50.2, 47.0, 42.9, 41.9, 41.3, 16.2, 13.7.
7-exo-Acetoxy-4-(chloromethyl)-4-hydroxytricy-
clo[3.3.0.02,8]octan-3-one (21); Typical Procedure
A soln of 9a (0.110 g, 0.45 mmol) in degassed acetone (110 mL,
solvent as well as sensitizer) was irradiated with a Hg vapor lamp
(125 W, Applied Photophysics) in a Pyrex immersion well for 4 h,
under N2. Acetone was removed under vacuum and the residue was
chromatographed (silica gel, PE–EtOAc, 85:15) to afford 21 (0.050
g, 45%) as a colorless liquid.
HRMS (ESI): m/z [M + H]+ calcd for C16H19O3S: 291.1055; found:
291.1055.
Ethyl 7-exo-Butoxy-3-oxotricyclo[3.3.0.02,8]octane-4-carboxyl-
ate (25)
IR (neat): 3524, 1736 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.84 (t, J = 6.9 Hz, 1 H), 3.64 (part
of AB pattern, J = 11.3 Hz, 1 H), 3.57 (part of AB pattern, J = 11.3
Hz, 1 H), 3.06 (br s, 1 H), 2.99 (dd, J1 = 8.0, J2 = 5.1 Hz, 1 H), 2.76
(dd, J1 = 10.2, J2 = 5.1 Hz, 1 H), 2.62 (dd, J1 = 13.1 Hz, J2 = 6.2 Hz,
1 H), 2.21 (ddd, J1 = 16.1 Hz, J2 = 10.6 Hz, J3 = 5.8 Hz, 2 H), 2.06
(s, 3 H), 2.02–1.90 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 209.5, 170.2, 83.0, 74.2, 49.7,
43.9, 39.1, 36.9, 30.9, 30.7, 21.0.
HRMS (ESI): m/z [M + Na]+ calcd for C11H13ClNaO4: 267.0400;
found: 267.0410.
NaH (0.450 g of 60% w/w suspension in oil, excess) was placed in
a dry two-necked flask and mineral oil was washed with anhyd PE.
Anhyd THF (20 mL) and ethyl carbonate (1.0 mL, 8.26 mmol) were
added. The mixture was heated to reflux and a soln of 22 (0.200 g,
1.03 mmol) in anhyd THF (10 mL) was added dropwise over a pe-
riod of 30 min at r.t. After the addition was complete, the mixture
was allowed to reflux for 2 h. The mixture was then cooled and
quenched by careful addition of H2O. The mixture was diluted with
H2O and extracted with EtOAc (3 × 50 mL). The combined extracts
were washed with H2O and brine and dried (anhyd Na2SO4). The
solvent was removed under reduced pressure and residue was puri-
fied by column chromatography (PE–EtOAc, 9:1) to give 25 (0.150
g, 56%) as a colorless liquid.
7-exo-Butoxytricyclo[3.3.0.02,8]octan-3-one (22)
Following the typical procedure for 21, irradiation of a soln of 16
(0.105 g, 1.54 mmol) in acetone (110 mL) for 2 h followed by re-
moval of the solvent and chromatography (PE–EtOAc, 93:7) gave
22 (0.048 g, 44%) as a colorless liquid.
IR (neat): 1726 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.24–4.12 (m, 2 H), 3.83 (super-
imposed dd, J = 6.5 Hz, 1 H), 3.54–3.36 (m, 2 H), 3.20–3.14 (m, 1
H), 3.03 (dd, J1 = 10.6, J2 = 5.1 Hz, 1 H), 2.79 (s, 1 H), 2.18–2.15
(m, 2 H), 2.06–2.0 (m, 2 H), 1.60–1.54 (m, 2 H), 1.42–1.33 (m, 2
H), 1.30–1.24 (m, 3 H), 0.96–0.88 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 207.4, 168.5, 79.5, 70.3, 64.5,
61.8, 46.4, 43.5, 40.6, 37.4, 36.1, 34.5, 32.0, 19.4, 14.2 (signals due
to major isomer).
IR (neat): 1742 cm–1.
1H NMR (400 MHz, CDCl3): d = 3.85 (superimposed dd, J = 7.69
Hz, 1 H), 3.54–3.38 (m, 2 H), 2.96–2.88 (m, 1 H), 2.82 (dd,
J1 = 10.9 Hz, J2 = 5.4 Hz, 1 H), 2.49 (dd, J1 = 17.9 Hz, J2 = 9.5 Hz,
1 H), 2.12–1.98 (m, 3 H), 1.75 (d, J = 17.9 Hz, 1 H), 1.58–1.52 (m,
3 H), 1.42–1.32 (m, 2 H), 0.92 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 214.7, 79.4, 70.2, 47.8, 47.8,
HRMS (ESI): m/z [M + H]+ calcd for C15H23O4: 267.1596; found:
36.8, 35.6, 35.4, 32.0, 19.4, 14.0.
267.1601.
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

PAPER
Cycloaddition of Cyclohexa-2,4-dienones and Transformation of Adducts
2727
Ethyl 7-exo-Butoxy-3-oxobicyclo[3.3.0]octane-2-carboxylate
(26) and Its Enol Tautomer 27
Prep. Proced. Int. 1999, 31, 617. (d) Magdziak, D.; Meek,
S. J.; Pettus, T. R. R. Chem. Rev. 2004, 104, 1383; and
references therein.
To a stirred soln of 25 (0.550 g, 2.075 mmol) in anhyd benzene (15
mL), AIBN 0.100 g, 0.609 mmol) and Bu3SnH (2.0 mL, 7.42 mmol)
were added and the mixture was refluxed for 12 h (TLC) under N2.
Benzene was removed and the residue was column chromato-
graphed (silica gel). First PE eluted the tin impurity, then PE–
EtOAc (92:8) eluted 26 and 27 (0.40 g, 73%) as a colorless liquid.
(3) (a) Liao, C.-C. Pure Appl. Chem. 2005, 77, 1211.
(b) Chang, S. Y.; Huang, S.-L.; Villarante, N. R.; Liao,
C.-C. Eur. J. Org. Chem. 2006, 4648. (c) Chittimalla, S. K.;
Hsiao, F.-Y.; Liao, C.-C. Org. Biomol. Chem. 2006, 4,
2267. (d) Liao, C.-C.; Wei, C. P. Tetrahedron Lett. 1989, 30,
2255.
IR (neat): 1751, 1723, 1658 cm–1.
(4) (a) Bonnarme, V.; Bachmann, C.; Cousson, A.; Mondon,
M.; Gesson, J.-P. Tetrahedron 1999, 55, 433.
1H NMR (400 MHz, CDCl3) (keto–enol mixture): d = 10.44 (br s, 1
H), 4.30–4.10 (m, 4 H), 4.04–3.94 (m, 1 H), 3.90–3.80 (m, 1 H),
3.44–3.30 (m, 5 H), 3.22–3.10 (m, 1 H), 3.02–2.92 (m, 1 H), 2.84–
2.60 (m, 3 H), 2.28–2.06 (m, 4 H), 2.02–1.90 (m, 2 H), 1.76–1.64
(m, 2 H), 1.54–1.42 (m, 5 H), 1.40–1.20 (m, 12 H), 0.95–0.88 (m, 6
H).
13C NMR (100 MHz, CDCl3): d = 212.6, 174.5, 170.1, 169.4, 104.4,
80.9, 80.6, 68.7, 68.6, 61.5, 61.4, 59.8, 57.8, 44.3, 43.2, 42.9, 42.7,
39.9, 39.5, 39.3, 39.0, 38.4, 36.2, 34.4, 32.2, 32.1,19.5, 14.4, 14.2,
13.9.
(b) Bonnarme, V.; Mondon, M.; Cousson, A.; Gesson, J.-P.
Chem. Commun. 1999, 1143. (c) Gesson, J.-P.; Hervaud, L.;
Mondon, M. Tetrahedron Lett. 1993, 34, 2941.
(5) (a) Singh, V. Acc. Chem. Res. 1999, 32, 324. (b) Singh, V.;
Pal, S.; Mobin, S. M. J. Org. Chem. 2006, 71, 3014.
(c) Singh, V.; Pal, S.; Tosh, D. K.; Mobin, S. M. Tetrahedron
2007, 63, 2446.
(6) (a) Toyota, M.; Asano, T.; Ihara, M. Org. Lett. 2005, 7,
3929. (b) Banwell, M. G.; Edwards, A. J.; Harfoot, G. J.;
Jolliffe, K. A. Tetrahedron 2004, 60, 535. (c) Srikrishna,
A.; Satyanarayana, G. Org. Lett. 2004, 6, 2337.
HRMS (ESI): m/z [M + H]+ calcd for C15H25O4: 269.1753; found:
269.1740.
(d) Hagiwara, H.; Morii, A.; Yamada, Y.; Hoshi, T.; Suzuki,
T. Tetrahedron Lett. 2003, 44, 1595. (e) Paquette, L. A.;
Guevel, R.; Sakamoto, S.; Kim, I. H.; Crawford, J. J. Org.
Chem. 2003, 68, 6096. (f) Spiegel, D. A.; Njardarson, J. T.;
Wood, J. L. Tetrahedron 2002, 58, 6545. (g) Tisdale, E. J.;
Chowdhury, C.; Vong, B. G.; Li, H.; Theodorakis, E. A.
Org. Lett. 2002, 4, 909.
7-exo-Butoxybicyclo[3.3.0]octan-3-one (28)
To a stirred soln of 22 (0.490 g, 2.52 mmol) in anhyd benzene (20
mL), AIBN (0.100 g, 0.609 mmol) and Bu3SnH (1.0 mL, 3.71
mmol) were added and the mixture was refluxed for 12 h (TLC) un-
der N2. Benzene was removed and the residue was column chro-
matographed (silica gel). First PE eluted the tin impurity then (PE–
EtOAc, 96:4) eluted 28 (0.330 g, 67%) as a colorless liquid.
(7) (a) Kim, M.; Gais, H.-J. J. Org. Chem. 2006, 71, 4642.
(b) Sheddan, N. A.; Mulzer, J. Org. Biomol. Chem. 2006, 4,
4127. (c) Sheddan, N. A.; Mulzer, J. Org. Lett. 2006, 8,
3101. (d) Sheddan, N. A.; Mulzer, J. Org. Lett. 2005, 7,
5115.
(8) (a) Bergen, M. V.; Gais, H.-J. J. Am. Chem. Soc. 2002, 124,
4321. (b) Lerm, M.; Gais, H.-J.; Cheng, K.; Vermeeren, C.
J. Am. Chem. Soc. 2003, 125, 9653. (c) Okamoto, S.;
Subburaj, K.; Sato, F. J. Am. Chem. Soc. 2000, 122, 11244.
(9) (a) Das, S.; Chandrashekhar, S.; Yadav, J. S.; Gree, R.
Chem. Rev. 2007, 107, 3286. (b) Schinzer, D.
IR (neat): 1741 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.03–3.96 (m, 1 H), 3.36 (super-
imposed dd, J = 6.5 Hz, 2 H), 2.94–2.82 (m, 2 H), 2.58–2.46 (m, 2
H), 2.22–1.96 (m, 4 H), 1.64–1.48 (m, 4 H), 1.42–1.30 (m, 2 H),
0.91 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 220.7, 81.3, 68.6, 44.7, 39.7,
37.7, 32.2, 19.5, 14.0.
HRMS (ESI): m/z [M + H]+ calcd for C12H21O2: 197.1542; found:
Carbacyclins: Stable Analogues of Prostacyclins, In
Organic Synthesis Highlights II; Waldman, H. E., Ed.;
VCH: New York, 1995, 301. (c) Collins, P. W.; Djuric, S.
W. Chem. Rev. 1993, 93, 1533.
197.1543.
Acknowledgment
(10) (a) Paquette, L. A.; Doherty, A. M. Polyquinane Chemistry,
Vol. 26; Hafner, K.; Rees, C. W.; Trost, B. M.; Lehn, J.- M.;
Schleyer, P. v. R.; Zahradnik, R., Eds.; Springer Verlag:
Berlin, 1987. (b) Mehta, G.; Srikrishna, A. Chem. Rev. 1997,
97, 671. (c) Jung, M. E.; Maderna, A. Tetrahedron Lett.
2005, 46, 5057. (d) Hagiwara, H.; Endou, S.; Fukushima,
M.; Hoshi, T.; Suzuki, T. Org. Lett. 2004, 6, 1115.
(e) Kraus, G. A.; Kim, J. Tetrahedron Lett. 2004, 45, 1457.
(11) (a) Ito, H.; Hasegawa, M.; Takenaka, Y.; Kobayashi, J.;
Iguchi, K. J. Am. Chem. Soc. 2004, 126, 4520.
(b) Anderson, R. J.; Taglialatela-Scafati, O.; Deo-Jangra, U.;
Campbell, N.; Roberge, M. Org. Lett. 2002, 4, 4085.
(12) (a) Adler, E.; Brasen, S.; Miyake, H. Acta Chem. Scand.
1971, 25, 2055. (b) Adler, E.; Holmberg, K. Acta Chem.
Scand., Sect. B 1974, 28, 465. (c) Singh, V.; Bedekar, A. V.
Synth. Commun. 1989, 19, 107.
(13) Crystal data 7b: C13H19O3Cl, MW 258.09, space group,
monoclinic, P21/c, a = 10.256(2), b = 7.6274(12),
c = 15.360(7) Å, a = 90.0, b = 107.44(3), g = 90.0°,
U = 1146.3(6) A3, Z = 4, Dc = 1.218 g/m3, T = 293(2) K,
F(000) = 456, size = 0.26 × 0.16 × 0.12 mm. Reflections/
collected/unique 10532/2012 [R(int) = 0.0258], final R
indices [I >2s(I)] = R1 = 0.0369, wR2 = 0.105c, R indices
We are thankful to SAIF for spectral facility. Continued financial
support from DST New Delhi is gratefully acknowledged. One of
us (G.C.) is thankful to CSIR, New Delhi for a research fellowship.
Thanks are due to DST for creating a National Single Crystal X-ray
Diffraction facility and FIST grant for mass spectral facility.
References:
(1) (a) Carruthers, W. Cycloaddition Reactions in Organic
Synthesis; Pergamon Press: Oxford, 1990. (b) Nicolaou, K.
C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G.
Angew. Chem. Int. Ed. 2002, 41, 1668. (c) Stocking, E. M.;
Williams, R. M. Angew. Chem. Int. Ed. 2003, 42, 3078.
(d) Oikawa, H.; Tokiwano, T. Nat. Prod. Rep. 2004, 21,
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2005, 105, 4779.
(2) (a) Lebrasseur, N.; Gagnepain, J.; Ozanne-Beaudenon, A.;
Leger, J.-M.; Quideau, S. J. Org. Chem. 2007, 72, 6280.
(b) Gagnepain, J.; Castel, F.; Quideau, S. Angew. Chem. Int.
Ed. 2007, 46, 1533. (c) Quideau, S.; Pouysegu, L. Org.
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York

2728
V. Singh et al.
PAPER
(all data) R1 = 0.0554, wR2 = 0.1107. The complete crystal
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif quoting the CCDC number 674959.
(15) (a) Demuth, M.; Hisken, W. Angew. Chem., Int. Ed. Engl.
1985, 24, 973. (b) Demuth, M.; Schaffner, K. Angew.
Chem., Int. Ed. Engl. 1982, 21, 820. (c) Yates, P.; Burnell,
D. J.; Freer, V. J.; Sawyer, J. F. Can. J. Chem. 1987, 65, 69.
(d) Padwa, A.; Zhi, L.; Fryxel, G. E. J. Org. Chem. 1991, 56,
1077.
(14) Crystal data 11c: C17H19ClO4S, MW 354.83, space group,
monoclinic, P21/c, a = 8.3197(6), b = 23.0608(19),
c = 15.360(7) Å, a = 90.0, b = 96.045(6), g = 90.0°,
U = 1600.8(2) A3, Z = 4, Dc = 1.472 mg/m3, T = 120(2) K,
F(000) = 744, size = 0.33 × 0.27 × 0.21 mm. Reflections/
collected/unique 8932 / 2801 [R(int) = 0.0732], final R
indices [I >2s(I)] = R1 = 0.0826, wR2 = 0.2139, R indices
(all data) R1 = 0.0965, wR2 = 0.2226. The complete crystal
data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif quoting the CCDC number 674960.
(16) (a) Zimmerman, H. E.; Armesto, D. Chem. Rev. 1996, 96,
3065. (b) Armesto, D.; Ortiz, M. J.; Agarrabeitia, A. R. In
CRC Handbook of Organic Photochemistry and
Photobiology; Horspool, W.; Lenci, F., Eds.; CRC Press:
Boca Raton FL, 2004, 95.1.
(17) Singh, V. In CRC Handbook of Organic Photochemistry and
Photobiology; Horspool, W.; Lenci, F., Eds.; CRC Press:
Boca Raton FL, 2004, 78.1.
(18) Enholm, E. J.; Jia, Z. J. J. Org. Chem. 1997, 62, 174.
(19) (a) Park, H.; Lee, Y. S. Bull. Korean Chem. Soc. 1993, 14,
86. (b) Node, M.; Inoue, T.; Araki, M.; Nakamura, D.;
Nishide, K. Tetrahedron Lett. 1995, 36, 2255.
Synthesis 2008, No. 17, 2719–2728 © Thieme Stuttgart · New York